WO-A-00/36405 discloses an apparatus and method for characterising libraries of different materials using X-ray scattering. The apparatus includes an X-ray beam directed at the library, which library contains an array of elements each containing a different material, a chamber which houses the library and a beam line for directing the X-ray beam onto the library in the chamber. During the characterisation, the X-ray beam scatters off of the element and a detector detects the scattered X-ray beam in order to generate characterisation data for the element.
U.S. Pat. No. 6,111,930 discloses an X-ray diffractometer suitable for detection in reflection mode as well as transmission mode. In the reflection mode the support for an analyte is in horizontal position. In order to perform an analysis in transmission mode the support is rotated about a horizontal axis of the goniometer, so that the support is in an essentially vertical position.
Scattering of incident radiation such as X-rays, gamma rays, cathode rays, etc. from a sample of material can yield information about the atomic structure of the material. When such a beam of radiation strikes a sample, a pattern of diffracted radiation is created, which has a spatial intensity distribution that depends on the wavelength of the incident radiation and the atomic structure of the material and that can be recorded on a suitable detector. Diffraction analysis is the method of choice for studying crystalline materials, crystallisation behaviour and liquid, gel or solid phase, or phase transitions of materials.
Crystallisation is in general considered as the separation or precipitation out of a liquid environment or the settling into the solid phase of a melt. The basic approach to crystallisation of substance from a solution is usually fairly simple. The molecule(s) to be crystallised is (are) dissolved or suspended and subsequently subjected to conditions that affect the solubility of the molecule or molecular complex in solution. This can be achieved by removal of the solvent or by the addition of other compounds that reduce the solubility, optionally in combination with variation of other factors such as temperature, pressure or gravitational forces. When the conditions are right, small nuclei will form from which crystals will grow. However, the relations between the crystallisation conditions and the crystal packing or even the occurrence of crystallisation is generally not well understood. The optimisation of the crystallisation conditions and the identification of conditions that lead to one specific type of molecular packing in the crystal are largely based on trial and error. The determination of the optimal crystallisation conditions can therefore be a laborious and time-consuming process.
When many different samples have to be submitted to diffraction analysis, the efficiency of the analysis is of the utmost importance. By far the most efficient way of analysis in terms of amount of sample required, measuring time and signal-to-noise ratio is the transmission geometry of diffraction. In the transmission diffraction mode, the entire fan of forwardly diffracted radiation is measured by a position sensitive radiation detector, unlike in the reflection mode, where only a small section of the fan of diffracted radiation is measured. However the transmission geometry of powder diffraction is hardly ever used, since it can be compromised by strong absorption in the case of very electron dense samples. Also, very thin analyte films have to be used to obtain a suitable resolution. Nevertheless, many organic samples, like drugs or drug candidates, are sufficiently transparent not to compromise the quality of the powder diffraction data. In these and many other cases, applying the transmission geometry to such samples will substantially reduce the measuring time required to obtain a signal-to-noise ratio that is sufficient for further characterisation. To increase throughput, an automated array, allowing for fast measuring of many analytes without human interference, is highly desirable. To this end, a convenient way of mounting all samples simultaneously in an array format, and automatically translating said array during the analysis from one sample to the next can be employed.
In all set-ups for diffraction in the transmission geometry that have been used up till now, as is also the case in WO-A-00/36405, the radiation beam is horizontal and the analyte support mounted substantially vertical, implying that any sample either needs to be bonded by some physical means to a (semi-)translucent substrate, or enclosed in a container, e.g. a thin-walled glass or quartz capillary. In this “horizontal” set-up the analytes that are formed during a certain experiment have to be removed to another container for transmission diffraction analysis. This can be inconvenient, because it is time-consuming, and it involves an extra processing step. Removal of an analyte further involves risks of the crystallised structure of the analyte being disrupted, or the analyte being contaminated. Furthermore, it is not convenient to study phase transitions of the analyte using the known apparatus, when one of the phases is liquid as the analyte may drop off or shift relative to the radiation beam.
Furthermore, until presently, for successful crystallisation to take place, a large amount of analyte is required.
The above problems are particularly pertinent in the case of e.g. the early development of new substances or in high throughput experimentation wherein often only a very small amount of analyte is available. High throughput experimentation is known in the art and is used for simultaneously conducting a large number of experiments using a plurality of vessels, optionally with different reaction conditions. High throughput experimentation is used for instance in the pharmaceutical industry for discovery and development of new and useful drugs and in the field of catalysts for the development of new catalysts.